Ramon Ramirez (1-0) earned his first win in a Red Sox uniform, and Jonathan Papelbon pitched the ninth for his third save.
Though Fenway Park continues to be a house of horrors for the Baltimore pitching staff, it's not exactly a warm place for Penny.
He was making his first start before the home fans, and it couldn't have gone much worse. He allowed eight runs and six hits over three-plus innings, walking five and fanning just one while allowing a grand slam to Nick Markakis.
"We had Hunter Jones up real early when we started to score," manager Terry Francona said. "Penny actually stayed out there another inning. We got Manny Delcarmen up, we made it 7-5, and he put zeroes up and it allowed us to get back in the game."
"Tonight, those guys coming back like that, that's a first for me," said Penny. "Other teams I've played on, down 7-0 in the second, it's over. You feel a lot better about an outing like that when the team comes back and wins the game."
With none out and one on in the fourth, Delcarmen was the first to enter the game in relief, and he was outstanding. The first batter he faced, Markakis, doubled in a run, then he retired the next eight batters he faced.
"I felt bad for them," Penny said. "I'm supposed to still be out there. They did a great job tonight coming in. A starter that goes three [innings], that's not a good thing for the bullpen. Those guys came in there and threw the ball really well."
Including Friday, Penny has allowed 17 earned runs over eight innings in two career starts at Fenway.
Penny surrendered a harmless one-out double in the first, but the Orioles did some major damage in the second, sending 10 batters to the plate. After bases-loaded walks to Ryan Freel and Adam Jones, Markakis took advantage of a hanging 0-1 curveball and drove it several rows into the center-field bleachers for his second career grand slam.
"It was a good pitch, and he went down and got it," Penny said. "I felt great. I haven't had that kind of stuff in a while. The walks killed me tonight."
Penny labored through the second, throwing 40 of his 85 pitches in that inning alone.
The Red Sox immediately showed life when they got to Jeremy Guthrie in the bottom of the second for four runs, highlighted by Jason Bay's two-run homer to the Orioles' bullpen in right. Guthrie needed 36 pitches to get through the second.
Drew's homer to right was the only run of the third, when the Red Sox closed to within two runs. After Baltimore tacked on a run in the fourth thanks to a double by Markakis, for his fifth RBI of the night, the Red Sox scored three in the fifth. The rally included a two-run double to deep center by Nick Green that tied the game and chased Guthrie.
The game also included a very scary moment in the fateful sixth, when Baez drilled Kevin Youkilis in the head with a fastball. Youkilis was fine, and he would come around to score Boston's 10th run on Mike Lowell's RBI single.
Ramirez entered to start the sixth and retired the first four batters he faced before allowing one-out singles to Brian Roberts and Jones in the eighth. Hideki Okajima came through with his finest outing of the season, getting Markakis to fly out to deep center for the second out and fanning Aubrey Huff with the tying runs in scoring position to end the threat.
"The bullpen did a tremendous job of keeping them in the game," said Orioles manager Dave Trembley. "That was the difference in the game."
This wasn't the first time the Orioles lost a big lead and a game with Guthrie on the mound. Guthrie was the starter when the Red Sox executed the "Mother's Day Miracle" on May 13, 2007, scoring six runs in the bottom of the ninth to win, 6-5.